Biomedical subjects

R R Bell

Publications and source records attributed to R R Bell.

At least 19 recordsLinked to original sources

PubMed2004

Evaluation of the long-term pancreatic effects of constitutive nitric oxide synthase inhibition in dogs.

Constitutive and inducible isoforms of nitric oxide synthase (NOS) catalyze the synthesis of nitric oxide (NO) from L-arginine in various tissues and in different pathophysiologic states. Short-term treatment with NOS inhibitors has been associated with pancreatic enzyme elevations and pancreatic acinar cell degeneration; however, long-term pancreatic effects of NOS inhibition are not known. The purpose of this study was to evaluate the subchronic pancreatic effects of L-nitro-arginine (LNA), a compound that preferentially inhibits constitutive NOS isoforms. LNA was administered orally at doses of 10 and 30 mg/kg per day to 6 female dogs/group for 4 weeks. To differentiate whether the pancreatic effects of LNA may be related to its arginine structure, an additional group was given L-arginine (L-Arg) at plasma concentrations similar to the high dose of LNA (30 mg/kg per day). Pancreatic effects were monitored by changes in serum levels of pancreatic enzymes at regular intervals and by microscopic examinations at the end of the study. Both LNA and L-Arg were systematically available throughout the 4-week study period. LNA produced dose-related elevations (1.3-10-fold above concurrent control) in serum levels of pancreatic enzymes (amylase, lipase and trypsin-like immunoreactivity) during the 4-week treatment period with peak elevations occurring during the first week. Histologic assessments of the pancreas conducted at the end of the 4-week dosing period were unremarkable. Additionally, LNA treatment resulted in reduction in heart rate (40%), gastric distension and gastric mucosal erosion and ulceration. No pancreatic, cardiac, or gastric effects were seen with L-Arg, indicating that above effects were likely due to NOS inhibition. Results of this study confirmed previous observations of acute pancreatic alterations following the inhibition of constitutive NOS isoforms. However, these pancreatic alterations appear to be only transient effects as elevations in serum enzymes declined over time and no structural acinar cell damage was seen after continuous treatment with LNA for 4 weeks, suggesting an adaptation to NOS inhibition over time.

Amylases↗

PubMed2003

Expression of cyclooxygenase-2 in embryonic and fetal tissues during organogenesis and late pregnancy.

BACKGROUND: Cyclooxygenase (COX) catalyzes the committed step in prostaglandin biosynthesis and exists as two related but unique isoforms, COX-1 (constitutive) and COX-2 (inducible). Prostaglandins (PGs) are known to have many important functions in reproduction, such as placentation and decidualization. Studies with the COX-1 and COX-2 knockout mice have demonstrated that COX-2, but not COX-1, is crucial for normal ovulation, implantation, and decidualization, suggesting that COX-2-derived PGs are important during the initial stages of pregnancy. Although the COX-2 knockout mice did not exhibit any abnormalities at birth, relatively little information exists with regard to the expression of COX-2 in the fetus during development. METHODS: In order to understand the role of COX-2 throughout pregnancy, we characterized the cell type and the temporal expression of inducible COX-2 throughout embryonic and fetal development in the rat (n = 22) by immunohistochemistry and in situ hybridization. RESULTS: High levels of COX-2 expression were seen in decidualized uterine tissue on gestation days 7-13 and then in the fetal membranes on gestation days 17-20. Cyclooxygenase-2 expression was not detectable in any tissues from developing embryos during gestation days 7-13, but was observed in the fetal growth period (gestation days 15-20) in the skin, heart, cartilage, and the kidney. CONCLUSIONS: No COX-2 expression was seen in fetal tissues at days 7-13 of gestation, but was seen in various tissues at days 15-17 of gestation. These observations suggest that COX-2 may be important in mid to late pregnancy through an effect on fetal organ growth, but not in the organogenetic phase of fetal development.

Animals↗

PubMed2001

A contemporaneous finding of fenproporex in a polydrug suicide.

Fenproporex is a sympathomimetic agent with a pharmacological profile similar to that of amphetamine. It is available in many countries throughout the world, but it is currently not available in the United States. Because of its stimulant effects, it has a great potential for abuse. To the best of our knowledge, there have been no literature reports of blood or serum concentrations found in therapeutic, toxic, or fatal cases. We report a case where fenproporex was a finding in the death of a young adult. Blood, urine, and gastric contents were analyzed. The following drug concentrations were found: 0.90 mg/L (inferior vena cava blood), 1.2 mg/L (urine), and 120 mg total (gastric) for fenproporex and 0.084 mg/L (inferior vena cava blood), 0.94 mg/L (urine), and 0.14 mg total (gastric) for amphetamine. In addition to the fenproporex, other medications detected and their blood concentrations found in this case were H diazepam (0.54 mg/L), nordiazepam (0.46 mg/L), diphenhydramine (0.12 mg/L), and gamma hydroxybutyric acid (GHB) (1100 mg/L).

Adult↗

PubMed2000

Intratracheal exposure of the guinea pig lung to cadmium and/or selenium: a histological evaluation.

Anesthetized male Hartley guinea pigs (350-410 g) (n=5) received intratracheally, saline; cadmium (Cd) (0.3 mg); selenium (Se) (0.3 or 0.06 mg); or Cd (0.3 mg) with Se (0.06 mg), per animal. Twenty-four hours later, lungs were evaluated. Bronchoalveolar-lavage fluid of Cd- and/or Se-treated animals varied in their total and differential leukocyte percent population from that of saline control (P<0.05). Cadmium alone or with Se caused high lung to body weight ratios (P<0.05). High lung wet-weight to dry-weight (W/D) ratios (P<0.05) suggestive of lung edema, were evident after Cd and/or Se exposure. Histological examination of Cd- and/or Se-exposed lungs revealed leukocytic infiltration. Results demonstrated that separate or concurrent exposure to noxious metal(s) such as Cd and Se provoke lung edema and injury. Low dose of Se which when instilled alone, although did not result in an increased W/D lung ratio, failed to subside concurrently administered Cd-inflicted damage.

Animals↗

PubMed1999

An acute intratracheal selenium study: immediate effects on respiration in guinea pigs.

Pulmonary function was assessed in non-sensitized male guinea pigs (206-445 g) before and after intratracheal (ITr) treatment with saline or selenium (Se, 0.06 mg/100 g body weight) as selenium dioxide (SeO2) or seleno-L-methionine (SeM). Pulmonary functional parameters such as the respiratory rate (f), tidal volume (TV), dynamic lung compliance (Cdynl) and lung resistance (Rl) were determined using the respiratory flow (F) signal and the transpulmonary signal obtained via the intrapleural pressure (P) from the animal. Although, pulmonary dysfunction was observable with exposure to two different Se compounds, the SeO2-induced changes in f and Rl were significant (P < 0.05). Treatment with SeM did not result in alteration of any of the parameters significantly. Results indicated that acute ITr SeO2 exposure affects respiration precipitated by a significantly decreased f and an increased Rl unlike after SeM. The Cdynl did not change significantly after treatment with either of the two Se compounds. Comparing the immediate effects of the two different Se compounds on respiration, acute ITr SeO2 exposure was found to be more detrimental to pulmonary function than SeM.

Animals↗

PubMed1998

Guinea pig pulmonary mechanics: altered sensitivity to carbachol by cadmium and/or selenium.

Male Hartley guinea pigs (480-610 g) were treated intratracheally as follows: saline, cadmium (Cd, 0.3 mg), selenium (Se, 0.3 or 0.06 mg), or Se (0.06 mg) and Cd (0.3 mg) simultaneously. Selenium and Cd were administered as sodium selenite and cadmium chloride, respectively. Twenty-four h later, dynamic lung compliance (Cdyn) and pulmonary resistance (Rp) were measured before (baseline Cdyn and Rp) and after carbachol administration (0.0001, 0.001, 0.01, and 0.1 mumol/kg, intravenously). Results indicated a significant decrease in baseline Cdyn caused by 0.3 mg of Cd, 0.3 mg or 0.06 mg of Se, and 0.3 mg of Cd with 0.06 mg of Se (p < 0.05). A significant increase in baseline Rp due to 0.3 mg of Se was observed (p < 0.05). Carbachol decreased Cdyn significantly below baseline, evident after lower doses of carbachol, in guinea pigs pretreated with 0.3 mg of Se, whereas a significant improvement in Cdyn was seen after 0.0001 mumol/kg carbachol in the group pretreated with Se and Cd simultaneously (p < 0.05) compared with the respective baseline values of the saline-treated group. Similarly, a significant increase in Rp was observed after carbachol in groups pretreated with 0.3 mg of Cd or Se (p < 0.05). Results also indicated a significant increase in large airway constriction caused by Cd and/or Se (p < 0.05). A leftward shift in the carbachol dose-response curve indicated increased sensitivity to carbachol in Cd- and/or Sepretreated guinea pigs.

Animals↗

PubMed1997

Selenium and cadmium induced pulmonary functional impairment and cytotoxicity.

Ovalbumin-sensitized (50 mg/kg, i.p.) male Hartley-guinea-pigs (550-610 g; n = 6) were treated 14 days later intratracheally with saline, cadmium (Cd 0.3 mg), selenium (Se 0.3 mg or 0.06 mg) or Se (0.06 mg) with Cd (0.3 mg). After 24 h, baseline dynamic-lung-compliance (Cdynl) and pulmonary-resistance (Rp), and percent change after ovalbumin-aerosol-challenge (10 mg/ml, 60 s) were assessed. Cadmium or Se (0.3 mg), Se (0.06 mg) and/or Cd (0.3 mg) decreased Cdynl (P < 0.05). Selenium (0.3 mg) increased Rp (P < 0.05). Ovalbumin-challenge decreased Cdynl and increased Rp in all groups. Analysis of bronchoalveolar-lavage-fluid (BALF) displayed increased activities of lactate-dehydrogenase (LDH), beta-glucuronidase (beta-G), alkaline-phosphatase (AP), and protein due to 0.3 mg Se, 0.3 mg Cd alone or with 0.06 mg Se (P < 0.05). Findings indicated that, 0.3 mg Se is more detrimental than 0.3 mg Cd to lung-dynamics despite a modest protection by 0.06 mg Se against Cd illustrated by an ameliorated Cdynl and lower protein in BALF.

Animals↗

PubMed1997

Voluntary exercise and monounsaturated canola oil reduce fat gain in mice fed diets high in fat.

High fat diets increase body fat stores. The following experiment was undertaken to determine whether the type of dietary fat could influence fat storage and whether voluntary exercise could prevent diet-induced obesity in mice fed high fat diets. Sixty-nine 6-wk-old female mice were fed one of three diets: low fat (11.5% of energy from fat), beef fat (40.8% of energy from fat) or canola oil (40.8% of energy from fat). In each diet group, 13 mice had free access to activity wheels in their cages (exercising), and the remaining 10 mice were housed in standard mouse cages (nonexercising). Body weight and body composition were measured before and after 8 wk of treatment. The nonexercising mice fed beef fat weighed more and had significantly more body fat (23.2 +/- 2.5 g/100 g body wt) than mice fed the low fat or canola oil diet (13.9 +/- 1.7 and 16.8 +/- 1.9 g/100 g body wt, respectively). Voluntary exercise did not affect lean body mass but did result in significantly lower body fat in all diet groups (beef, 12.6 +/- 0.9; low fat, 7.4 +/- 0.6; canola oil, 9.6 +/- 1.4 g/100 g body wt). The amount of body fat of mice fed the monounsaturated canola oil was significantly less than that of mice fed the beef fat diet, suggesting that the type of fat as well as the amount of fat influences body fat stores. Furthermore, voluntary exercise decreased body fat in all mice and prevented diet-induced obesity in mice fed diets high in fat.

Animals↗

PubMed1997

Cadmium and/or selenium effects on guinea pig lung PGE2, TXB2 and LTC4.

Male Hartley guinea pigs (480-610 g; n=5) were treated intratracheally with saline, cadmium (Cd, 0.3 mg) as cadmium chloride, selenium (Se, 0.3 or 0.06 mg) as sodium selenite or Se (0.06 mg) and Cd (0.3 mg). After 24 hours, lungs were collected and analyzed for prostaglandin (PGE2), thromboxane (TXB2) and leukotriene (LTC4) levels. Results indicated that, 0.3 mg Se and 0.06 mg Se in combination with 0.3 mg Cd increased PGE2 significantly. Selenium and Cd alone or in combination, decreased LTC4 and TXB2 significantly.

Animals↗

PubMed1995

Diet-induced obesity in mice can be treated without energy restriction using exercise and/or a low fat diet.

Diet-induced obesity was treated with a high carbohydrate, low fat diet and/or increased voluntary exercise in mice. All mice had free access to food and water during the two stage experiment. In Stage 1, 20 female mice were fed a high carbohydrate diet and 50 were made obese by consumption of a diet providing 40.8% of energy from fat. At the end of Stage 1, obese mice had significantly greater body fat stores (22.9 +/- 0.9 g/100 g body wt) than mice fed the high carbohydrate diet (12.9 +/- 1.2) (P < 0.001), yet there was no significant difference in lean body mass. In Stage 2, half of the mice were given activity wheels to increase their voluntary activity and half of the obese mice were switched to a high carbohydrate diet resulting in six groups with treatment designations of obese or lean; exercise or nonexercise, and carbohydrate or fat diets. Body fat was significantly reduced by consumption of the high carbohydrate diet (P < 0.005) and by exercise (P < 0.001), but neither treatment affected lean body mass. Exercising mice consumed significantly more energy than nonexercising mice, yet experienced a decrease in body fat and energy stores.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Selenium lethality: role of glutathione and metallothionein.

Male Sprague-Dawley rats (200-300 g) were pretreated (i.p.) with diethylmaleate (DEM; 3.1 mmol/kg) or propylene glycol (PG). After 1 h, three PG and three DEM groups received saline or sodium selenite (Se: 0.8 or 1.6 mg/kg) i.p. Eighty to one hundred percent mortality occurred within 3 h after Se in DEM-pretreated groups. Except for one PG and one DEM group, which were sacrificed after 1 h, the remaining groups received saline or Se (1.6 mg/kg) 25 h after pretreatment. No mortality occurred within 3 h after Se. Liver and kidney GSH decreased at 1 h, while liver MT increased at 28 h. The changes are related to Se-induced lethality.

Animals↗

PubMed1991

Effect of in vitro treatment of rat hepatocytes with selenium, and/or cadmium on cell viability, glucose output, and cellular glutathione.

The effects of cadmium as cadmium acetate and selenium as sodium selenite on glucose output, cell viability, and glutathione levels in rat hepatocytes were evaluated. Isolated hepatocytes (200 mg wet wt cells) derived from naive male Sprague--Dawley rats (210-260 g) were incubated at 37 degrees C, with sodium acetate (C2H3NaO2; NaAc) 12.5 microM, 6.3 microM, 3.2 microM; cadmium acetate (C4H6CdO4; Cd) 12.5 microM, 6.3 microM, 3.2 microM; sodium selenite (Na2SeO3; Se) 25 microM, 12.5 microM, 6.3 microM; or Se (6.3 microM) and Cd (3.2 microM). After an incubation period of 2 h, glucose output, cell viability, and reduced glutathione (GSH) levels were determined. The results obtained indicate that incubation of hepatocytes with Se (12.5 or 25 microM) or Cd (3.2, 6.3, or 12.5 microM) resulted in a significant decrease in glucose output, cell viability, and glutathione levels (P less than 0.05) when compared to those incubated with NaAc (control). Selenium in concentrations of 6.3 microM decreased glutathione levels and cell viability only. The damaging effects induced by Cd on hepatocytes were significantly greater than those induced by Se. The decrease in glutathione levels observed following Cd treatment was considerably lowered when Se was concurrently added to the incubation medium. These findings suggest that Se may in part protect against the deleterious effects of Cd on hepatocytes.

Animals↗

PubMed1990

Acute effects of cadmium and selenium on glucose output from rat liver hepatocytes using various gluconeogenic precursors.

Male Sprague-Dawley rats (250-310 g) fasted for 24 h were injected i.p. with either sodium acetate (C2H3NaO2; 1.23 mg/kg, 15 mumol/kg), cadmium acetate (C4H6CdO4; 0.84 mg/kg, 3.6 mumol/kg), sodium selenite (Na2SeO3; 1.6 mg/kg, 9.2 mumol/kg) or cadmium acetate (0.84 mg/kg, 3.6 mumol/kg) and sodium selenite (1.6 mg/kg, 9.2 mumol/kg) simultaneously. Rats were sacrificed 180 min post-treatment and hepatocytes were isolated. An average of 85% cell viability was achieved. Hepatocyte suspension (50 mg cell wt/ml, 1 ml/tube) was incubated for 180 min at 37 degrees/C with 10 mM of one of the following substrates: beta-D(-)fructose, glycerol, DL-alanine, L(+)lactic acid or pyruvic acid. Glucose concentration of the supernatant was measured by a colorimetric method. Cadmium decreased glucose output significantly (P less than 0.05), when lactic acid or alanine was used as substrate, but did significantly (P less than 0.05) increase the output when pyruvic acid, glycerol or fructose was used. Selenium alone significantly increased (P less than 0.05) hepatic glucose output only when fructose was used as substrate. Selenium and cadmium concurrently administered significantly increased (P less than 0.05) hepatic glucose output when pyruvic acid, glycerol or fructose was used as substrate as compared to sodium acetate (control), cadmium or selenium alone. These findings suggest that cadmium and selenium affect the hepatic gluconeogenic pathway and that their effects depend on the gluconeogenic precursor used.

Animals↗

PubMed1990

Effect of cadmium on blood glucose level in the rat.

The purpose of this study was to determine the effect of cadmium (Cd) or Cd and selenium (Se) administered simultaneously on plasma glucose level. Male Sprague-Dawley derived rats (180-300 g), maintained under controlled environmental conditions, were segregated into fed and 24-h fasted groups prior to experimentation. Each group consisted of 3 subgroups which received one of the following treatments intraperitoneally: sodium acetate (NaAc) (1.23 mg/kg), Cd (0.84 mg/kg) or a combination of Se and Cd (1.6 and 0.84 mg/kg respectively). Plasma glucose was measured before and 30, 60, 120, 180, 240, 300 or 360 min after treatment. Results indicate that both Cd and concurrent administration of Se and Cd induce hyperglycemia in fed and fasted rats.

Acetates↗

PubMed1984

The influence of dietary citrate on the absorption and retention of orally ingested lead.

The influence of dietary citrate on the toxicity of orally ingested lead was investigated in male weanling mice. Twenty-four animals were divided into three equal groups. Group 1 served as controls, groups 2 and 3 were given 20 micrograms lead (as lead acetate) per g/diet, group 3 also received 4% sodium citrate in the diet. After 5 weeks, blood and tissue lead levels were measured. All mice given lead-supplemented diets had higher concentrations of lead in blood, liver, kidney, brain and bone than the control group, but the increase was significantly greater in the group given 4% sodium citrate in the diet. This work demonstrated that dietary citrate at levels which can be present in food significantly increases lead toxicity.

Animals↗

PubMed1984

Effects of dietary protein and exercise on brown adipose tissue and energy balance in experimental animals.

The effects of exercise and of dietary protein level on energy metabolism and brown adipose tissue (BAT) activity were investigated in weaning male mice. Mice were fed diets providing low (7.5%), adequate (12.5%) or high (25%) levels of dietary protein. Half of the animals in each dietary group were given moderate exercise by swimming. The lower the level of dietary protein, the greater the increase in food intake, energy expenditure, body fat and BAT mass; however, total-carcass energy, food efficiency and BAT activity were not affected by the level of dietary protein. In experiment 2, BAT was compared in mice swimming at 33 degrees C and 36 degrees C with non-exercised controls. In a third experiment, energy balance and BAT activity were compared in rats exercised at 36 degrees C and in paired weight gain (PWG) rats whose food intake was restricted to achieve weight gains equal to that of the exercised rats. PWG rats maintained carcass energy content equal to that of the controls and significantly greater than the exercised rats by decreasing energy expenditure. Moderate exercise did not affect food intake, whereas rigorous exercise decreased energy intake. Exercise did not affect BAT mass or thermogenic activity; however, mild cold stress did increase BAT activity. Exercise decreased body fat, carcass energy and food efficiency without affecting BAT.

Adipose Tissue, Brown↗

PubMed1983

The influence of dietary fat on the toxicity of orally ingested lead in rats.

The influence of dietary fat on the toxicity of orally ingested lead was investigated. Groups of ten male weanling Wistar rats were maintained on diets providing 11.5, 20, 40 or 60% of energy from fat for 8 wk. All diets were supplemented with a low level of lead--1.25 mg Pb (as lead acetate) per 1000 kJ energy in the diet. Groups receiving 11.5 and 20% of energy as fat had similar lead levels for each tissue studied. Raising the fat level to 40 or 60% of energy resulted in significant increases in tissue-lead concentrations with each increment in dietary fat. The groups receiving 60% of energy as fat had more than twice the level of lead in the femur, kidney, liver and brain than the control rats maintained on the diet containing 11.5% energy as fat, even though the amount of lead ingested was the same for all groups. delta-Aminolaevulinic acid dehydratase activity was not affected when dietary fat was increased from 11.5 to 20%. There was a significant reduction in activity when fat was increased to 40 or 60% of energy. Free erythrocyte protoporphyrin was not affected by the level of dietary fat. This work demonstrates that increasing the level of dietary fat significantly increases lead toxicity and indicates the need for further research on the interaction between dietary factors and lead toxicity.

Administration, Oral↗

PubMed1983

The influence of dietary phosphate on the toxicity of orally ingested lead in rats.

The influence of elevated dietary phosphate on the toxicity of orally ingested lead was investigated in male weanling Wistar rats. Two groups of 20 rats were fed diets containing either adequate (0.5%) or high (1.2%) levels of phosphorus (as phosphates). Half of the rats on each level of phosphorus were given 20 micrograms lead (as lead acetate)/g dry diet. After 8 wk, biochemical tests for lead toxicity were carried out and tissue-lead levels were measured. All of the rats given lead-supplemented diets had higher concentrations of lead in bone, brain, kidney and liver than those given diets without added lead but the increase was significantly greater in all tissues in the group given the 1.2% phosphorus diet. Lead supplementation increased the levels of free erythrocyte protoporphyrin and decreased the activity of delta-aminolaevulinic acid dehydratase. The lead-induced increase in the level of free erythrocyte protoporphyrin was no greater in the high-phosphate group than in the low-phosphate group but the decrease in delta-aminolaevulinic acid dehydratase activity was significantly larger in the high-phosphate group. This work demonstrates that excess dietary phosphate significantly increases lead toxicity and indicates the need for continued research on the interaction between dietary factors and lead toxicity.

Analysis of Variance↗